Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Unraveling the link between atopic dermatitis and autoimmune diseases in children: Insights from a large-scale cohort study with 15-year follow-up and shared gene ontology analysis.

BACKGROUND: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. METHODS: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. RESULTS: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23-1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. CONCLUSIONS: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

Intense Near-Infrared Light-Emitting NaYF4:Nd,Yb-Based Nanophosphors for Luminescent Solar Concentrators.

In this study, we synthesized NaYF4-based downshifting nanophosphors (DSNPs), and fabricated DSNP-polydimethylsiloxane (PDMS) composites. Nd3+ ions were doped into the core and shell to increase absorbance at 800 nm. Yb3+ ions were co-doped into the core to achieve intense near-infrared (NIR) luminescence. To further enhance the NIR luminescence, NaYF4:Nd,Yb/NaYF4:Nd/NaYF4 core/shell/shell (C/S/S) DSNPs were synthesized. The C/S/S DSNPs showed a 3.0-fold enhanced NIR emission at 978 nm compared with core DSNPs under 800 nm NIR light. The synthesized C/S/S DSNPs showed high thermal stability and photostability against the irradiation with ultraviolet light and NIR light. Moreover, for application as luminescent solar concentrators (LSCs), C/S/S DSNPs were incorporated into the PDMS polymer, and the DSNP-PDMS composite containing 0.25 wt% of C/S/S DSNP was fabricated. The DSNP-PDMS composite showed high transparency (average transmittance = 79.4% for the visible spectral range of 380-750 nm). This result demonstrates the applicability of the DSNP-PDMS composite in transparent photovoltaic modules.

Nanoparticle-Based Chimeric Antigen Receptor Therapy for Cancer Immunotherapy.

Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) has emerged as an innovative immunotherapy for hematological cancer treatment. However, the limited effect on solid tumors, complex processes, and excessive manufacturing costs remain as limitations of CAR-T therapy. Nanotechnology provides an alternative to the conventional CAR-T therapy. Owing to their unique physicochemical properties, nanoparticles can not only serve as a delivery platform for drugs but also target specific cells. Nanoparticle-based CAR therapy can be applied not only to T cells but also to CAR-natural killer and CAR-macrophage, compensating for some of their limitations. This review focuses on the introduction of nanoparticle-based advanced CAR immune cell therapy and future perspectives on immune cell reprogramming.

Elemental-Migration-Assisted Full-Color-Tunable Upconversion Nanoparticles for Video-Rate Three-Dimensional Volumetric Displays.

Herein, we demonstrate video-rate color three-dimensional (3D) volumetric displays using elemental-migration-assisted full-color-tunable upconversion nanoparticles (UCNPs). In the heavily doped NaErF4:Tm-based core@multishell UCNPs, erbium migration was observed. By tailoring this migration through adjustment of the intermediate shell thickness between the core and the sensitizer-doped second shell, red-green orthogonal upconversion luminescence (UCL) was achieved. Furthermore, highly efficient red-green-blue orthogonal UCL and full-color tunability were achieved in the UCNPs through a combination of elemental-migration-assisted color tuning and selective photon blocking. Finally, 3D volumetric displays were fabricated using a UCNP-polydimethylsiloxane composite. More specifically, 3D color images were created and motion pictures based on the expansion, rotation, and up/down movement of the displayed images were realized in the display matrix. Overall, our study provides new insights into upconversion color tuning and the achievement of motion pictures in the UCNP-polydimethylsiloxane composite is expected to accelerate the further development of solid-state full-color 3D volumetric displays.

Nonstoichiometric LaO0.65F1.7 Structure and Its Green Luminescence Property Doped with Bi3+ and Tb3+ Ions for Applying White UV LEDs.

Red-green-blue phosphors excited by ultraviolet (UV) radiation for white light LEDs have received much attention to improve the efficiency, color rendering index (CRI), and chromatic stability. The spectral conversion of a rare-earth ion-doped nonstoichiometric LaO0.65F1.7 host was explored with structural analysis in this report. The nonstoichiometric structure of a LaO0.65F1.7 compound, synthesized by a solid-state reaction using La2O3 and excess NH4F precursors, was analyzed by synchrotron X-ray powder diffraction. The crystallized LaO0.65F1.7 host, which had a tetragonal space group of P4/nmm, contained 9- and 10-coordinated La3+ sites. Optical materials composed of La1-p-qBipTbqO0.65F1.7 (p = 0 and 0.01; q = 0-0.2) were prepared at 1050 °C for 2 h, and the single phase of the obtained phosphors was indexed by X-ray diffraction analysis. The photoluminescence spectra of the energy transfer from Bi3+ to Tb3+ were obtained upon excitation at 286 nm in the nonstoichiometric host lattice. The desired Commission Internationale de l'Eclairage (CIE) values of the phosphors were calculated. The intense green La0.89Bi0.01Tb0.1O0.65F1.7 phosphor with blue and red optical materials was fabricated on a 275 nm UV-LED chip, resulting in white light, and the internal quantum efficiency, CRI, correlated color temperature, and CIE of the pc LED were characterized.

Flexible 3D Nanonetworked Silica Film as a Polymer-Free Drug-Eluting Stent Platform to Effectively Suppress Tissue Hyperplasia in Rat Esophagus.

Loading and eluting drugs on self-expandable metallic stents (SEMSs) can be challenging in terms of fabrication, mechanical stability, and therapeutic effects. In this study, a flexible 3D nanonetworked silica film (NSF) capable of withstanding mechanical stress during dynamic expansion is constructed to function as a drug delivery platform on an entire SEMS surface. Despite covering a broad curved area, the synthesized NSF is defect-free and thin enough to increase the stent strut diameter (110 µm) by only 0.4 percent (110.45 µm). The hydrophobic modification of the surface enables loading of 4.7 times the sirolimus (SRL) concentration in NSF than Cypher, polymer-coated commercial stent, which is based on the same thickness of coating layer. Furthermore, SRL-loaded NSF exhibits a twofold delay in release compared to the control group without NSF. The SRL-loaded NSF SEMS significantly suppresses stent-induced tissue hyperplasia than the control SEMS in the rat esophagus (all variables, p < 0.05). Thus, the developed NSF is a promising polymer-free drug delivery platform to efficiently treat esophageal stricture.

Tumor Microenvironment Modulating Functional Nanoparticles for Effective Cancer Treatments.

Cancer is one of the major diseases that threaten human life worldwide. Despite advances in cancer treatment techniques, such as radiation therapy, chemotherapy, targeted therapy, and immunotherapy, it is still difficult to cure cancer because of the resistance mechanism of cancer cells. Current understanding of tumor biology has revealed that resistance to these anticancer therapies is due to the tumor microenvironment (TME) represented by hypoxia, acidity, dense extracellular matrix, and immunosuppression. This review demonstrates the latest strategies for effective cancer treatment using functional nanoparticles that can modulate the TME. Indeed, preclinical studies have shown that functional nanoparticles can effectively modulate the TME to treat refractory cancer. This strategy of using TMEs with controllable functional nanoparticles is expected to maximize cancer treatment efficiency in the future by combining it with various modern cancer therapeutics.

Impact of left atrial appendage closure on cardiac functional and structural remodeling: A difference-in-difference analysis of propensity score matched samples.

BACKGROUND: Although the safety and efficacy of left atrial (LA) appendage (LAA) closure (LAAC) in nonvalvular atrial fibrillation (NVAF) patients have been well documented in randomized controlled trials and real-world experience, there are limited data in the literature about the impact of LAAC on cardiac remodeling. The aim of the study was to examine the impact of LAAC on cardiac functional and structural remodeling in NVAF patients. METHODS: Between March 2014 and November 2016, 47 NVAF patients who underwent LAAC were included in this study (LAAC group). A control group (non-LAAC group) was formed from 141 NVAF patients without LAAC using propensity score matching. The difference-in-difference analysis was used to evaluate the difference in cardiac remodeling between the two groups at baseline and follow-up evaluations. RESULTS: The LAAC group had a larger increase in LA dimension, volume and volume index than the non-LAAC group (+3.9 mm, p = 0.001; +9.7 mL, p = 0.006 and +5.9 mL/m2, p = 0.011, respectively). Besides, a significant increase in E and E/e' ratio was also observed in the LAAC group (+14.6 cm/s, p = 0.002 and +2.3, p = 0.028, respectively). Compared with the non-LAAC group, left ventricular (LV) ejection fraction and fractional shortening decreased in LAAC patients, but were statistically insignificant (-3.5%, p = 0.109 and -2.0%, p = 0.167, respectively). CONCLUSIONS: There were significant increases in LA size and LV filling pressure among NVAF patients after LAAC. These impacts of LAAC on cardiac functional and structural remodeling may have some clinical implications that need to be addressed in future studies.

Combined Percutaneous Procedure in Patient with Lutembacher Syndrome: A Case Report and Real-World Experience Review.

Even cardiac surgery has been accepted as the standard therapy for Lutembacher syndrome, a combination of congenital ostium secundum atrial septal defect (ASD) and acquired mitral valve stenosis (MVS), it also owns many limitations and disadvantages. Therefore, seeking for a less invasive therapy with the same efficacy may be worthwhile. Thanks to the development in technology and experience gaining in cardiovascular intervention, the combination of the two proved effective procedures, including percutaneous MVS treatment using balloon valvuloplasty and percutaneous ASD closure using atrial septal occluders, can be utilized as an attractive alternative therapy for these conditions. Here, we present a successful percutaneous intervention in Lutembacher syndrome using the combination of mitral balloon valvuloplasty and ASD device closure and thoroughly review the experience of using this combined procedure existing in the literature.

Licorice isoliquiritigenin dampens angiogenic activity via inhibition of MAPK-responsive signaling pathways leading to induction of matrix metalloproteinases.

The aberrant expression of matrix metalloproteinases (MMPs) has been implicated in matrix degradation leading to angiogenesis. This study examined the inhibitory effects of isoliquiritigenin (ISL) on phorbol myristate acetate (PMA)-induced MMP production and its tissue inhibitor of MMP (TIMP) in endothelial cells. No induction of either necrotic or apoptotic cell death was observed in response to a treatment with ISL at or=1 microM while diminishing the elevated MMP-2 transcript level. In addition, ISL inhibited PMA-triggered migration and tube formation in a dose-dependent manner. ISL further increased the TIMP production up-regulated by PMA with a biphasic effect on TIMP-2 expression. This study further attempted to investigate whether a c-Jun N-terminal kinase (JNK)- or p38 mitogen-activated protein kinase (MAPK)-responsive mechanism was responsible for the MMP production and whether ISL disturbed these signaling pathways. PMA stimulated signaling of JNK and p38 MAPK, which was dampened by >or=10 microM ISL. These results demonstrate that ISL blocked JNK- or p38 MAPK-responsive pathways leading to direct MMP activation of PMA-exposed endothelial cells. Therefore, the ISL inhibition of MMP may boost a therapeutic efficacy during angiogenesis.

Blockade of vascular angiogenesis by Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujuba.

The matrix metalloproteinases (MMP) play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. Increased expression of MMP was observed in benign tissue hyperplasia and in atherosclerotic lesions. Invasive cancer cells utilize MMP to degrade the extracellular matrix and vascular basement membrane during metastasis, where MMP-2 has been implicated in the development and dissemination of malignancies. The present study attempted to examine the antiangiogenic activity of the medicinal herbs of Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujube (tAgR and tZj) with respect to MMP-2 production and endothelial motility in phorbol 12-myristate 13-acetate (PMA)- or VEGF-exposed human umbilical vein endothelial cells (HUVEC). Nontoxic tAgR and tZj substantially suppressed PMA-induced MMP-2 secretion. In addition, 25 microg/mL tAgR and tZj prevented vascular endothelial growth factor-stimulated endothelial cell transmigration and tube formation. The results reveal that tAgR and tZj dampened endothelial MMP-2 production leading to endothelial transmigration and tube formation. tAgR and tZj-mediated inhibition of endothelial MMP may boost a therapeutic efficacy during vascular angiogenesis.

Blockade of oxidized LDL-triggered endothelial apoptosis by quercetin and rutin through differential signaling pathways involving JAK2.

Oxidized LDL is highly atherogenic, as it stimulates foam cell formation and promotes inflammatory and thrombotic processes. The present study elucidated whether the antioxidants quercetin and its rutinoside rutin exert antiapoptosis in endothelial cells exposed to Cu(2+)-oxidized LDL. Quercetin and rutin inhibited the oxidized LDL-induced endothelial toxicity at nontoxic doses of

Blockade of chronic high glucose-induced endothelial apoptosis by Sasa borealis bamboo extract.

Hyperglycemia is a causal factor in the development of diabetic vascular complications including impaired vascular smooth muscle contractility and increased cell proliferation. The present study was designed to investigate the effects of Sasa borealis water-extract (SBwE) on chronic hyperglycemia-induced oxidative stress and apoptosis in human umbilical endothelial cells (HUVEC). HUVEC were cultured in 5.5 mM low glucose, 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control, or 33 mM high glucose for 5 days in the absence and presence of 1-30 microg/ ml SBwE. Caspase-3 activation and Annexin V staining revealed chronic high glucose-induced endothelial apoptotic toxicity with a generation of oxidants detected by DCF-fluorescence, and these effects were reversed by SBwE at > or =1 microg/ml in a dose-dependent manner. Cytoprotective SBwE substantially reduced the sustained high glucose-induced expression of endothelial nitric oxide synthase and attenuated the formation of peroxynitrite radicals. The suppressive effects of SBwE were most likely mediated through blunting activation of PKC beta 2 and NADPH oxidase promoted by high glucose. In addition, this bamboo extract modulated the high glucose-triggered mitogen-activated protein kinase-dependent upregulation of heat-shock proteins. Our results suggest that SBwE suppressed these detrimental effects caused by PKC-dependent peroxynitrite formation via activation of NADPH oxidase and induction of nitric oxide synthase and heat-shock protein family that may be essential mechanisms responsible for increased apoptotic oxidative stress in diabetic vascular complications. Moreover, the blockade of high glucose-elicited heat-shock protein induction appeared to be responsible for SBwE-alleviated endothelial apoptosis. Therefore, SBwE may be a therapeutic agent for the prevention and treatment of diabetic endothelial dysfunction and related complications.

(-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: involvement of mitogen-activated protein kinase.

Ultraviolet (UV) irradiation leads to distinct changes in skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix most likely mediated by matrix metalloproteinases (MMP), collagenases. These changes in collagenous skin tissues have been suggested to be causes of the skin wrinkling observed in premature aging of the skin. This study mimicked the action of environmental ultraviolet on skin and investigated whether (-)epigallocatechin gallate (EGCG), a bioactive catechin component of green tea, mechanistically inhibited activation of MMP-1, MMP-8, and MMP-13 and destruction of collagen in UV-B irradiated human dermal fibroblasts by modulating cellular signaling pathways. Cell viability was moderately decreased by > or = 30% in human dermal fibroblasts treated with 100 mJ/cm2 UV-B, accompanying a substantial generation of reactive oxygen species evidenced by DCF staining. Western blot analysis and immunocytochemical staining revealed that EGCG markedly suppressed collagen degradation enhanced in UV-B-exposed human dermal fibroblast. Pre-treatment of fibroblasts with EGCG also inhibited UV-B-induced production of collagenases, MMP-1, MMP-8 and MMP-13, in a dose-dependent manner. In addition, EGCG rapidly and substantially hampered UV-B irradiation-induced activation of ASK-1 and phosphorylation of MAPK, JNK, p38 MAPK, and ERK1/2, in dermal fibroblasts. These results demonstrate that EGCG has abilities to hamper UV-B-induced collagenolytic MMP production via interfering with the MAPK-responsive pathways. Therefore, EGCG may be a potential agent for the prevention and treatment of skin photoaging.

Molecular characterization of a cDNA encoding copper/zinc superoxide dismutase from cultured cells of Manihot esculenta.

Superoxide dismutase (SOD) cDNA, mSOD2, encoding cytosolic copper/zinc SOD (CuZnSOD) cDNA was isolated from suspension-cultured cells of cassava (Manihot esculenta Crantz) by cDNA library screening, and its expression was investigated in relation to environmental stress. mSOD2 is 774 bp in length with an open reading frame (ORF) of 152 amino acids, corresponding to a protein of predicted molecular mass 15 kDa and a pI of 5.22. One copy of the mSOD2 gene was found to be present in the cassava genome by Southern analysis using an mSOD2 cDNA-specific probe. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed diverse expression patterns for the mSOD2 gene in various tissues of intact cassava plants, at various stages of the growth in suspension cultures, and in the leaf tissues exposed to different stresses. The mSOD2 gene was highly expressed in suspension-cultured cells and in the stems of intact plants. However, it was expressed at low levels in leaves and roots. During suspension cell growth, the mSOD2 transcript progressively increased during culture. Moreover, the mSOD2 gene in excised cassava leaves responded to various stresses in different ways. In particular, it was highly induced in leaf tissue by several abiotic stresses, including high temperature (37 degrees C), chilling (4 degrees C), methyl viologen (MV) exposure, and wounding treatment. These results indicate that the mSOD2 gene is involved in the antioxidative process triggered by oxidative stress induced by environmental change.